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RECRUITINGPhase 3INTERVENTIONAL

CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis

CLEOPATTRA: Effects of NNC6019-0001 Versus Placebo on Cardiovascular Outcomes in Participants With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This study will find out if a new medicine called NNC6019-0001 can help reduce the risk of heart-related death and illness in participants with a condition called transthyretin amyloid cardiomyopathy (ATTR-CM), which affects the heart. Participants will either receive NNC6019-0001 or a placebo (a treatment with no active medicine), and which one they get is decided by chance. Everyone in the study will continue receiving their usual heart treatments as recommended by their doctor.

Who May Be Eligible (Plain English)

Who May Qualify: - Male or female. - Age 18 years or above at the time of signing the willing to sign a consent form. - Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF. Note: Target ATTRv recruitment is approximately 15 percent of the study population. 1. Cardiac amyloid infiltration demonstrated by: - Cardiac biopsy positive for TTR amyloid, OR - Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) scintigraphy with single-photon emission computed tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR - Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE). Notes: - Non-invasive diagnostic pathway will be confirmed by a centralised expert review. - Bone tracer scintigraphy will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP). 2. Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm). 3. Chronic HF (New York Heart Association \[NYHA\] Class I-IV) requiring ongoing treatment with a loop diuretic with: - At least 1 documented hospitalisation for HF, OR - History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema). ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * Male or female. * Age 18 years or above at the time of signing the informed consent. * Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF. Note: Target ATTRv recruitment is approximately 15 percent of the study population. 1. Cardiac amyloid infiltration demonstrated by: * Cardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) scintigraphy with single-photon emission computed tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE). Notes: * Non-invasive diagnostic pathway will be confirmed by a centralised expert review. * Bone tracer scintigraphy will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP). 2. Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm). 3. Chronic HF (New York Heart Association \[NYHA\] Class I-IV) requiring ongoing treatment with a loop diuretic with: * At least 1 documented hospitalisation for HF, OR * History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema). * Expected to be on stable cardiovascular medical therapy (defined as no greater than 50 percent dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit. * Completed more than 50 meters on the 6MWT at screening. Exclusion Criteria: * Known or suspected hypersensitivity to study intervention(s) or related products. * Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy. * Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening. * Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis, known leptomeningeal amyloidosis, or multiple myeloma. * HF not primarily caused by ATTR-CM (e.g., due to hypertension, valvular heart disease, or ischemic heart disease in the opinion of the investigator). * Currently hospitalised or hospitalised within 14 days prior to screening. * Currently treated with positive inotropic medication. * Uncorrected, severe, haemodynamically significant, left-sided heart valve disease. Note: Pre-existing echocardiogram up to 2 years old may be used. * Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 60 days of screening. * Prior solid organ transplant or planned solid organ transplant during the study. * Left ventricular ejection fraction (LVEF) less than 30 percent as assessed by centralised review of echocardiography. * Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, carcinoma in situ/high-grade prostatic intraepithelial neoplasia \[PIN\], low-risk prostate cancer, or on stable therapy for prostate cancer) within 3 years before screening. * End-stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 mL/min/1.73 m\^2 at screening, or chronic/intermittent haemodialysis or peritoneal dialysis).

Treatments Being Tested

DRUG

NNC6019-0001

NNC6019-0001 will be administered IV.

DRUG

Placebo (NNC6019-0001)

Placebo matched to NNC6019-0001 will be administered IV.

Locations (20)

Mayo Clinic Hospital
Phoenix, Arizona, United States
University of California San Diego (UCSD) - Sulpizio Cardiovascular Center (SCVC)
La Jolla, California, United States
Keck School of Medicine USC - Healthcare Consultation Center 2 (HCCII)
Los Angeles, California, United States
Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, United States
UCI Medical Center
Orange, California, United States
Profound Research LLC at Southern California Heart Specialists
Pasadena, California, United States
University of California, San Francisco Medical Center
San Francisco, California, United States
Northbay Cardiology Inc.
Santa Rosa, California, United States
Lucile Packard Children's Hospital
Stanford, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
MedStar Heart & Vascular Institute (MHVI) - MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
UF Health Heart and Vascular Hospital
Gainesville, Florida, United States
Northeast Georgia Heart Center, Pc (Nghc)
Gainesville, Georgia, United States
The Queen's Medical Center
Honolulu, Hawaii, United States
Northwestern University Clinical and Translational Sciences Institute
Chicago, Illinois, United States
The University of Chicago Medicine
Chicago, Illinois, United States
Endeavor Health - Glenbrook Hospital
Glenview, Illinois, United States
Indiana University (IU) Health - Methodist Professional Center II
Indianapolis, Indiana, United States
LCMC - LSU University Medical Center New Orleans LCMC Center
New Orleans, Louisiana, United States
University of Maryland Medical Center (UMMC) - Children's Hospital (UMCH)
Baltimore, Maryland, United States